Surgical Implant and Process of Manufacturing Thereof

ABSTRACT

A surgical implant ( 20 ) comprises a flexible, areal basic structure ( 22 ) having a first face and a second face and being provided with pores ( 26 ) extending from the first face to the second face. A barrier layer ( 24 ) having a first face and a second face is placed, with its second face, at the first face of the basic structure ( 2 ) and attached to the basic structure ( 22 ). The barrier layer ( 24 ) is deformed into at least part of the pores ( 26 ) where it forms, in a respective pore ( 10 ), a barrier region ( 28 ).

The invention relates to a surgical implant, in particular for repair ofa tissue or muscle wall defect, such as a ventral hernia, and to aprocess of manufacturing such an implant.

Many ventral hernia repair implants comprise a surgical mesh and one ormore adhesion barrier layers to prevent the adhesion of internalstructures, like the intestine, to the mesh. For laparoscopic surgery,the surgeon has to roll the implant, pass it through a trocar sleeve andthen lift it up with the mesh side facing to the abdominal wall(parietal side) and the adhesion barrier of the implant facing to theinternal organs (viscera). Ideally, during the positioning of the meshon the peritoneum, there is no need for an additional aid and the meshsticks (clings) itself to the abdominal wall and can be easily fixatedwith clips or sutures to the abdominal wall.

The surgical implant Physiomesh® by Ethicon is a barrier/mesh compositeimplant which fulfils these optimal requirements. In Physiomesh®, a meshlayer is sandwiched between a barrier layer on the visceral side and anadditional film for achieving a clinging effect on the parietal side.

U.S. Pat. No. 8,579,990 B discloses a mesh laminate comprisingperforated polymer films on both sides of a surgical mesh. This surgicalimplant clings to the abdominal wall after laparoscopic placement,without the use of additional instruments.

WO 03/099160 A describes a surgical implant comprising a knobbed film,which can be connected to a mesh-like basic structure. The knobs of thefilm are manufactured in a step independent of a further step in whichthe knobbed film is attached to the basic structure. Generally, theknobs point away from the basic structure in order to minimize, by meansof the knobs, adhesion effects, and it would be difficult to align theknobs with the mesh pores for fitting the knobs into the mesh pores.

The object of the invention is the provision of a surgical implant, inparticular for repair of a tissue or muscle wall defect, which can beeasily handled during placement, which has barrier properties on thevisceral side, which requires a relatively small amount of materialonly, and which can be manufactured in an efficient manner. Inparticular, it would be desirable to be able to achieve a clingingeffect on the parietal side without the need for an additional film,which would allow for tissue integration on the parietal side andminimize the amount of material used for the implant.

This object is achieved by the surgical implant according to claim 1.Claim 19 relates to a process of manufacturing such a surgical implant.Advantageous versions of the invention follow from the dependent claims.

The surgical implant according to the invention comprises a flexible,areal basic structure having a first face and a second face (i.e., afirst side and a second side). The term “areal” means that the basicstructure is generally flat, i.e. that it has a relatively smallthickness, but because the basic structure is flexible it can bedeformed into the third dimension. The basic structure is provided withpores extending from the first face to the second face. The surgicalimplant further comprises a barrier layer having a first face and asecond face, which is placed, with its second face, at the first face ofthe basic structure and is attached to the basic structure. The barrierlayer is deformed into at least part of the pores where it forms, in arespective pore, a barrier region. In a barrier region, the second faceof the barrier layer may be closer to the second face of the basicstructure than the first face of the barrier layer is to the first faceof the basic structure.

The basic structure can be designed, e.g., as a surgical mesh, amesh-like sheet, a spacer fabric, a perforated film, a perforated woven,a perforated non-woven, or as a mesh pouch (e.g. as a surgical meshwherein part of the mesh is folded to form a pocket). An essentialfeature of the basic structure is the presence of pores which extendacross the thickness of the basic structure. The pores may have a size,e.g., in the range of from 1 mm to 9 mm. Herein, the size of a givenpore is defined as the greatest (free) width of that pore. It is alsopossible that the pores of a given basic structure have different sizesand/or different shapes. The barrier layer generally has ananti-adhesive effect and prevents bodily tissue from growing into thebasic structure via the first face thereof. It can be made from anabsorbable material so that these effects are temporarily, which permitsa control of the healing process after implantation. Starting from thefirst face of the basic structure, the barrier layer enters at leastpart of the pores and then extends, in the inner area of a poreconsidered, e.g. roughly at the level of the second face of the basicstructure or not far from that, to form a barrier region inside thatpore. In this way, the second face may get largely smooth, because thestructure determined by the second face of the basic structure may begenerally leveled by the barrier regions formed by the barrier layerinside the pores of the basic structure.

In many cases, the basic structure does not have plane surfaces on asmall-scale level, e.g. due to points where threads in a warp-knittedstructure cross each other. Therefore, it may be more convenient todefine the extent by which a barrier region in a pore of the basicstructure approaches the second face of the basic structure in terms ofa roughness which is averaged over a larger area of the surgicalimplant. To this end, a suitable measure is the average roughness, asdefined in ASME B46.1-2009 (and similarly in DIN EN ISO 25178-2). Inembodiments of the invention, the average roughness is measured overthat area of the basic structure where the barrier layer is deformedinto pores of the basic structure, and the average roughness is smallerat the second faces of the barrier layer and the basic structure than atthe first faces of the barrier layer and the basic structure.

Specifically, the ratio of the average roughness measured at the secondfaces of the barrier layer and the basic structure to the averageroughness measured at the first faces of the barrier layer and the basicstructure has a value in one of the following ranges: 0.0-0.1, 0.1-0.2,0.2-0.3, 0.3-0.4, 0.4-0.5, 0.5-0.6, 0.6-0.7, 0.7-0.8, 0.8-0.9, 0.9-1.0.

In Section 1-6.1 of ASME B46.1-2009, the average roughness S_(a) isdefined as

S _(a)=(1/A _(e))∫∫|Z(x,y)|dx dy

The integration is performed over x and y (area integral) in that regionof the basic structure where the barrier layer is deformed into pores ofthe basic structure. The total size of this area is A_(e). That means,if the barrier layer extends over all of the basic structure and if thebarrier layer deforms into all of the pores of the basic structure,A_(e) is the area of the basic structure. Z(x,y) is the function used torepresent the point-by-point deviations between the measured topologyand the mean surface (see 1-5.2 of ASME B46.1-2009; least squares meansurface). Z(x,y) varies between positive and negative values, for whichreason its absolute value |Z(x,y)| is taken to characterize theroughness. The mean surface at the first faces of the barrier layer andthe basic structure has to be determined independently of the meansurface at the second faces of the barrier layer and the basicstructure.

Since the average roughness is smaller at the second faces of thebarrier layer and the basic structure (i.e., measured from the side ofthe second faces) than at the first faces of the barrier layer and thebasic structure (i.e., measured from the side of the first faces), thesurgical implant is generally smoother at the side of the second faces.

In a laparoscopic repair procedure, the surgical implant according tothe invention clings well to the abdominal wall or the peritoneum(parietal side) if the second faces of the basic structure and thebarrier layer are oriented towards the peritoneum (and if a suitablematerial of the barrier layer is selected), because this second facesprovide a large contact area. If required, the implant can be easilyrepositioned, and it can be fixated by using fixation means likesutures, clips or surgical tacks. The clinging properties facilitate thesurgical procedure. At the first faces (visceral side), the barrierlayer prevents adhesions. Thus, the surgical implant according to theinvention provides or increases clinging properties to the peritoneumduring laparoscopic repair, without the use of additional film materialmounted at the second face of the basic structure (as in the prior art).The one barrier layer has a dual function: (1) adhesion barrier(visceral side) and (2) clinging aid (parietal side). The contact areaon the parietal side is increased without affecting the mesh-to-tissuecontact area, in contrast to prior-art implants comprising a full filmlayer at the parietal side. As the parietal side of the implant is notcovered by such an additional film layer, tissue integration from theparietal side is generally possible. Moreover, since the barrier layeris deformed into the pores of the basic structure, it can be stronglyattached to the basic structure.

Thus, in an example for a process of intraperitoneally placing thesurgical implant according to the invention in a patient's body, thesurgical implant is introduced into the body via a trocar sleeve and isdeployed, the second face of the basic structure facing the patient'speritoneum. Then the surgical implant clings to the peritoneum,generally without additional holding aids, and it can be fixed on theperitoneum, e.g. by sutures, clips and/or surgical tacks. The implantcan be used in open surgery as well.

The surgical implant according to the invention can be applied, e.g.,for repair of a tissue or muscle wall defect, such as a ventral hernia,but also as a hernia mesh in general, as a pelvic mesh, as a breastimplant support, as a patch for the dura mater, or as a reinforcementfor staple lines or suture lines in general surgery.

Another advantage of the surgical implant according to the invention isan easy and efficient way of manufacturing, see below.

In the pores of the basic structure comprising a region of the barrierlayer, this barrier region may be basically flat. Such a designcontributes to the smoothness of the second face in the surgicalimplant, as mentioned above. For example, deviations from ideal flatness(i.e. flat like a plane) may result in a ripple of less than 50 μm orless than 30 μm or less than 20 μm, which feels generally smooth inpalpation. The barrier region may have a size (defined as the greatestwidth of that basically flat barrier region in the pore contemplated) inthe range of, e.g., from 0.5 mm to 5 mm, depending on the size of therespective pore of the basic structure. The size of the barrier regionis less or slightly less than the respective pore size because thebarrier layer, from the edges of the barrier region, rises or steeplyrises in order to cover the material of the basic structure at the firstface of the basic structure.

The angle between a barrier region and a plane in parallel to the secondface of the basic structure may be, e.g., in the range of from 0° to 5°.When approaching the edges of the pore in question, the slope changesbecause the barrier layer has to adjust to the geometry of the basicstructure. In such regions, typical values for the slope are, e.g., inthe range of from 8° to 110°, or of from 10° to 50°.

Between pores of the basic structure, the barrier layer may form ridgeswhere the first face of the barrier layer rises above the first face ofthe barrier layer in an adjacent barrier region by an amount in therange of, e.g. from 50 μm to 900 μm. In this way, the first face of theimplant (i.e., the barrier layer side) can feel rougher than the secondface by palpation. These ridges may aid in an anti-adhesive effect ofthe barrier layer.

The barrier layer may be provided with pores having a smaller size thanthat of the pores of the basic structure.

Generally, the barrier layer may be continuous, in particular consistingof one piece of material, or it may be made of a plurality of spacedfilm pieces, e.g. of film pieces which do not touch each other or whichtouch just in common corners. However, each film piece would becontinuous over at least two or more pores of the basic structure.Generally, the barrier layer extends over material of the basicstructure (at the first face of the basic structure) and is notrestricted to zones just inside the pores.

In order to fix the barrier layer to the basic structure, a bondingmaterial can be used which has a melting temperature lower than themelting temperature of at least part of the material of the basicstructure and lower than the melting temperature of at least part of thematerial of the barrier layer. Depending on the materials of the basicstructure and of the barrier layer, a suitable bonding material maycomprise poly-p-dioxanone, which is absorbable. The bonding material canbe embodied, e.g., as filaments incorporated in threads used forwarp-knitting the basic structure, as threads of the basic structure, oras a film layer arranged between the basic structure and the barrierlayer during the shaping of the barrier layer (see below). In theprocess, the temperature is adjusted such that the bonding material getssoft and sticky to serve as a glue, while the basic structure and thebarrier layer are not misshaped in an uncontrolled way.

In advantageous embodiments of the invention, the basic structure islong-term stable. This can be achieved by non-absorbable materials,which generally are well known in the art. Examples of non-absorbablematerials are polyalkenes, polypropylene, polyethylene, fluorinatedpolyolefins, polytetrafluoroethylene, PTFE, ePTFE, cPTFE, polyvinylidenefluoride, blends of polyvinylidene fluoride and copolymers of vinylidenefluoride and hexafluoropropene, polyamides, polyimides, polyurethanes,polyisoprenes, polystyrenes, polysilicones, polycarbonates,polyarylether ketones, polymethacrylic acid esters, polyacrylic acidesters, aliphatic polyesters, aromatic polyesters, and mixtures of suchsubstances as well as copolymers of polymerizable substances of thatlist.

The basic structure may also comprise absorbable material or slowlyabsorbable material (i.e. material which, 90 days after implantation,still has at least 10% of its initial tensile strength), eitherexclusively or in addition to non-absorbable material, e.g. syntheticbioabsorbable polymer materials, polyhydroxy acids, polylactides,polyglycolides, copolymers of glycolide and lactide, copolymers ofglycolide and lactide in the ratio 90:10, copolymers of glycolide andlactide in the ratio 5:95, copolymers of lactide and trimethylenecarbonate, copolymers of glycolide, lactide and trimethylene carbonate,polyhydroxybutyrates, polyhydroxyvaleriates, polycaprolactones,copolymers of glycolide and ε-caprolactone, polydioxanones,poly-p-dioxanone, synthetic and natural oligo- and polyamino acids,polyphosphazenes, polyanhydrides, polyorthoesters, polyphosphates,polyphosphonates, polyalcohols, polysaccharides, polyethers, collagen,gelatin, bioabsorbable gel films cross-linked with omega 3 fatty acids,oxygenized regenerated cellulose, or mixtures of such substances.

The barrier layer may be designed as a polymeric film and may comprisean absorbable material, e.g. copolymers of glycolide and ε-caprolactone,collagens, gelatine, hyaluronic acid, polyvinyl pyrrolidone, polyvinylalcohol, fatty acids, polyhydroxy acids, polyether esters,polydioxanones, or mixtures or copolymers of polymerizable substancesthereof. However, a non-absorbable material of the barrier layer (or amixture of absorbable and non-absorbable materials) is conceivable aswell. The barrier layer may be transparent. Non-transparent embodimentsof the barrier layer are also possible.

As already mentioned, the barrier layer generally has an anti-adhesiveeffect and prevents bodily tissue from growing into the basic structurevia the first face thereof. As an anti-adhesive layer, it prevents orminimizes adhesion to internal body structures such as bowel, liver orspleen to the implant. Suitable films can be made from resorbablematerials, for example comprising poly-p-dioxanone (PDS®, Ethicon),copolymers of glycolide and ε-caprolactone (e.g., MONOCRYL®,(poliglecaprone 25), Ethicon) and/or copolymers of glycolide and lactide(in particular in the ratio 90:10; VICRYL® (polyglactin 910), Ethicon).Generally, a large variety of synthetic bioabsorbable polymer materialscan be used, for example polyhydroxy acids (e.g., polylactides,polyglycolides, polyhydroxybutyrates, polyhydroxyvaleriates),polycaprolactones, polydioxanones, and PEG- or PEO-esters thereof suchas PLGA-PEG-PLGA or Methoxypolyethyleneglycol-PLGA, synthetic (but alsonatural) oligo- and polyamino acids, polyphosphazenes, polyanhydrides,polyorthoesters, polyphosphates, polyphosphonates, polyalcohols,polysaccharides, polyethers, polycyanoacrylates (poly 2-OCA-co-BLCA) ascured from Ethicon's Omnex®. However, naturally occurring materials suchas fibrin, albumin, collagens and gelatine, hyaluronic acid or naturallyderived materials such as bioabsorbable gel films or gel forming films,cross-linked omega 3-fatty acids or oxygenized regenerated cellulose(ORC), crosslinked albumines or rh albumines where an albumin solutionis cross-linked and foamed/expanded, crosslinked products wherepolyethylene glycol (PEG) ester solution and a trilysine amine arecross-linked, are possible as well. Examples for non-resorbablematerials are PTFE sheet, fluorinated polyolefine (PVDF), copolymers ofvinylidene fluoride and hexafluoropropene, silicone, durable polyvinylalcohol gels, polyurethane.

It is also possible that the barrier layer comprises, at least in part,swelling or gel-forming substances. Such substances include surfactantssuch as PPO-PEO block copolymers (poloxamers), polysorbates, sorbitanesters (like sorbitan monolaurate, sorbitan monopalmitate, sorbitanmonostearate, sorbitan tristearate, sorbitan monooleate), phospholipids,hydophilic natural or synthetic polymers such as alginate, dextrane,chitosane, carracen, polyethylene glycol (PEG), soluble polyvinylalcohol(PVA), polyvinylpyrrolidone (PVP), carboxymethyl cellulose (CMC), HES(hydroxyethyl starch). Hydrogel-forming polymers may be obtained uponpolymerization or polyaddition or polycondensation containing at leastone of the substances selected from the following group: polymerizedhydroxyethyl methacrylate (HEMA), polymerized hydroxypropyl methacrylate(HPMA), polymerized α-methacryloyl-ω-methoxy polyethylene glycol,polymerized methacryloyloxyethyl phosphorylcholine (MPC), polyethyleneglycol-bisacrylate and copolymers thereof, cured resorbable pre-polymersof type A-B-C-B-A with commercial examples sold as Focalseal® (Genzyme)or Advaseal® (Ethicon) with A=acryl or methacryl groups,B=hydrolytically splittable groups containing polymers of lactide,glycolide, 2-hydroxybutyric acid, 2-hydroxyvaleriac acid, trimethylenecarbonate, polyorthoesters, polyanhydrides, polyphosphates,polyphosphazenes and/or polyamides and/or copolymers thereof, andC=hydrophilic polymers, in particular polyethylene glycol (PEG),polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP),poly-N-isopropylacrylamide (PNiPAAM).

Moreover, the surgical implant according to the invention may compriseat least one active ingredient and/or at least one contrast agent, e.g.incorporated in, applied to or adsorbed to the basic structure and/orprovided at a layer of the implant, e.g. incorporated in or adsorbed tothe barrier layer, and/or in encapsulated form.

Examples for active ingredients are biologically active or therapeuticingredients which can optionally be released locally after theimplantation. Substances which are suitable as active or therapeuticagents may be naturally occurring or synthetic, and include but are notlimited to, for example, antibiotics, antimicrobials, antibacterials,antiseptics, chemotherapeutics, cytostatics, metastasis inhibitors,antidiabetics, antimycotics, gynecological agents, urological agents,anti-allergic agents, sexual hormones, sexual hormone inhibitors,haemostyptics, hormones, peptide-hormones, antidepressants, vitaminssuch as Vitamin C, antihistamines, naked DNA, plasmid DNA, cationic DNAcomplexes, RNA, cell constituents, vaccines, cells occurring naturallyin the body or genetically modified cells. The active or therapeuticagent may be present in various forms including in an encapsulated formor in an adsorbed form. With such active agents, the patient outcome maybe improved or a therapeutic effect may be provided (e.g., better woundhealing, or inflammation inhibition or reduction).

One preferred class of active agents are antibiotics that include suchagents as gentamicin or ZEVTERA™ (ceftobiprole medocaril) brandantibiotic (available from Basilea Pharmaceutica Ltd., Basel,Switzerland). Other active agents that may be used are highly effectivebroad-band antimicrobials against different bacteria and yeast (even inthe presence of bodily liquids) such as octenidine, octenidinedihydrochloride (available as active ingredient in Octenisept®disinfectant from Schülke & Mayer, Norderstedt, Germany),polyhexamethylene biguanide (PHMB) (available as active ingredient inLavasept® from Braun, Switzerland), triclosan, copper (Cu), silver (Ag),nanosilver, gold (Au), selenium (Se), gallium (Ga), taurolidine,N-chlorotaurine, alcohol-based antiseptics such as Listerine® mouthwash,N-a-lauryl-L-arginine ethyl ester (LAE), myristamidopropyl dimethylamine(MAPD, available as an active ingredient in SCHERCODINE™ M),oleamidopropyl dimethylamine (OAPD, available as an active ingredient inSCHERCODINE™ O), and stearamidopropyl dimethylamine (SAPD, available asan active ingredient in SCHERCODINE™ S), fatty acid monoesters,taurolidine, and PHMB.

Another class of active agents are local anesthetics that include suchagents as: Ambucaine, Benzocaine, Butacaine, Procaine/Benzocaine,Chloroprocaine, Cocaine, Cyclomethycaine, Dimethocaine/Larocaine,Etidocaine, Hydroxyprocaine, Hexylcaine, Isobucaine, Paraethoxycaine,Piperocaine, Procainamide, Propoxycaine, Procaine/Novocaine,Proparacaine, Tetracaine/Amethocaine, Lidocaine, Articaine, Bupivacaine,Dibucaine, Cinchocaine/Dibucaine, Etidocaine, Levobupivacaine,Lidocaine/Lignocaine, Mepivacaine, Metabutoxycaine, Piridocaine,Prilocaine, Propoxycaine, Pyrrocaine, Ropivacaine, Tetracaine,Trimecaine, Tolycaine, combinations thereof, e.g., Lidocaine/prilocaine(EMLA) or naturally derived local anesthetics including Saxitoxin,Tetrodotoxin, Menthol, Eugenol and prodrugs or derivatives thereof.

Moreover, a contrast agent may be included in or on the surgical implantaccording to the invention. Such a contrast agent may be a gas orgas-creating substance for ultrasound contrast or for MRI contrast, suchas metal complexes like GdDTPA or superparamagnetic nanoparticles(Resovist™ or Endorem™) as taught in EP 1 324 783 B1, which isincorporated by reference. X-Ray visible substances might be included asshown in EP 1 251 794 B1 (incorporated by reference), including purezirconium dioxide, stabilized zirconium dioxide, zirconium nitride,zirconium carbide, tantalum, tantalum pentoxide, barium sulphate,silver, silver iodide, gold, platinum, palladium, iridium, copper,ferric oxides, not very magnetic implant steels, non-magnetic implantsteels, titanium, alkali iodides, iodated aromatics, iodated aliphatics,iodated oligomers, iodated polymers, alloys of substances thereofcapable of being alloyed.

The surgical implant according to the invention may also comprise anorientation marker adapted for distinguishing the first face of thebasic structure from the second face of the basic structure. Such anorientation marker can be made, e.g., from an absorbablepoly-p-dioxanone film dyed with the violet dye “D&C Violet No. 2” andlaminated to, e.g., the visceral side of the barrier layer (i.e., thefirst face of the barrier layer), which preferably is not dyed. If theorientation marker has an appropriate asymmetric shape, it will beeasily visible whether the implant is oriented correctly, with thebarrier layer facing the internal organs, or whether not. Alternatively,the orientation marker (or parts thereof) may be arranged at the secondface of the barrier layer, i.e. in between the basic structure and thebarrier layer.

In other embodiments, printing or spraying techniques are used to applythe marker to the barrier layer. For example, a coloring agent may beprepared by dissolving a dye and a polymer in a suitable solvent, andthen the marker is sprayed onto the outer face of the barrier layer,e.g. by using an air-brush technique or an ink-jet printer. Afterevaporation of the solvent, the marker is firmly connected to thebarrier layer.

Alternatively, the marker may be applied to the parietal side of thebasic structure (i.e., the second face of the basic structure). In thiscase, the clinging effect due to the barrier layer being deformed intothe pores of the basic structure will not be significantly affected ifthe marker is relatively small or flat.

In an advantageous embodiment, the surgical implant comprises a basicstructure designed as a macro-porous surgical mesh (about 1 mm to 9 mmmaximum extension within each pore) knitted from polypropylene(PROLENE®, Ethicon; non-absorbable) and poly-p-dioxanone (PDS®, Ethicon;absorbable) fibers. An absorbable film made of a copolymer of glycolideand ε-caprolactone (MONOCRYL® (poliglecaprone 25) suture polymer,Ethicon) is laminated to the first face of the basic structure, whereinit extends into the pores and serves as the barrier layer. Additionally,an orientation marker cut from a dyed poly-p-dioxanone film is fixed tothe barrier layer. The implant is generally flat and has a “mesh side”and a “film side”.

The surgical implant of this specific embodiment is a partiallyabsorbable, flexible composite mesh prosthesis intended for the repairof ventral or incisional hernias and other fascial defects, includinginguinal hernias. The implant can be placed in an IPOM (intra-peritonealonlay mesh) technique. After intra-peritoneal implantation, the implantis in a permanent tissue contact. It comes into contact with theperitoneum on the parietal side and with intra-abdominal organs on thevisceral side. In summary, the structural elements of the implant havethe following functions: (1) The non-absorbable polypropylene meshcomponent of the basic structure is used to reinforce or bridge defectsto provide extended support during and following wound healing. (2) Theabsorbable barrier layer of MONOCRYL® is intended to physically separatethe basic structure from underlying tissue and organ surfaces (asbowel/omentum) during the critical wound healing period until the basicstructure mesh is covered by a neoperitoneum, thereby reducing theextent and severity of unintended tissue attachment to the permanentmaterial of the basic structure. (3) And during laparoscopic placement,the textured pattern formed at the second face of the basic structure bythe mesh structure and by the regions of the barrier layer deformed intothe mesh pores provides good clinging properties so that the handling ofthe implant is much improved.

In a process of manufacturing the surgical implant according to theinvention, a flexible, areal basic structure having a first face and asecond face is provided, with pores extending from the first face to thesecond face. Moreover, a barrier layer having a first face and a secondface is provided. The basic structure is placed onto a hard support, thesecond face of the basic structure facing the support. The barrierlayer, with its second face, is placed onto the first face of the basicstructure. A pad is placed onto the barrier layer (i.e., onto its firstface), wherein the pad is softer than the support. Then, heat andpressure are applied, thereby softening the material of the barrierlayer, urging it into the pores of the basic structure, and attachingthe barrier layer to the basic structure. Afterwards, optionally notbefore the end of a preselected period of time, the temperature andpressure can be decreased. It is also possible to cool (e.g. actively orby waiting) the support and/or the pad, e.g. to a preselectedtemperature or for a preselected period of time, while the pressure isat least partially maintained, and decrease the pressure afterwards.

This process is very efficient because the barrier layer is textured andlaminated with the basic structure in just one step, wherein material ofthe barrier layer enters into the pores of the basic structure and isconnected to the basic structure at the same time. Thus, any problemsrelated to the matching of a pre-shaped barrier layer into the pores ofthe basic structure do not occur. The softer pad presses the material ofthe barrier layer into the pores and is depressed itself in areas wherematerial of the basic structure is present. Thus, the softer pad adjuststo the pore pattern of the basic structure. On the opposite side, thehard support ensures a largely smooth surface of the implant. Generally,all variants of the surgical implant according to the inventionexplained above, including those defined in terms of average roughness,may be manufactured by this process.

To improve the attachment between the barrier layer and the basicstructure, a bonding material can be used, which has a meltingtemperature lower than the melting temperature of at least part of thematerial of the basic structure and lower than the melting temperatureof at least part of the material of the barrier layer. Such a bondingmaterial melts or gets soft during the application of heat and pressure,thus acting as a kind of melt glue, whereas the basic structure and thebarrier sheet are still able to keep their desired shapes.

The bonding material may be included in the basic structure provided,e.g. in the form of filaments comprising poly-p-dioxanone. Alternatively(or additionally), the bonding material may be included in the barrierlayer provided, e.g. as a sub-layer comprising poly-p-dioxanone andlaminated to a sub-layer comprising barrier material having a highermelting point than poly-p-dioxanone.

When the above-referenced advantageous embodiment of the surgicalimplant is manufactured, in which the basic structure is knitted frompolypropylene and from poly-p-dioxanone fibers, the poly-p-dioxanonefibers serve as the bonding material. The basic structure can be knittedin a way that it is still a stable polypropylene mesh after thepoly-p-dioxanone component has lost its shape and structural functionduring the manufacturing process (and after it has been absorbed afterimplantation).

After applying heat and before the pressure is (completely) relieved,the basic structure and the barrier layer may be cooled (actively or bywaiting), e.g. via the support and/or the pad, as already mentionedabove. In this way, the barrier layer is “frozen” in its desired shapeand any bonding material can settle or harden so that the surgicalimplant acquires and keeps its final design.

In another process of manufacturing the surgical implant according tothe invention, the barrier layer is adhered to the basic structure byusing a pressure-sensitive adhesive, without applying heat. In thiscase, pressure can be exerted in a press between a hard support and asofter pad, wherein the pad urges the barrier layer into the pores ofthe basic structure (as in the former process) and the pressure alsoresults in a good adhesion of the barrier layer to the basic structure.

In the following, the invention is further explained by means ofexamples. The drawings show in

FIGS. 1A, 1B and 1C a schematic illustration of an embodiment of theprocess of manufacturing a surgical implant according to the invention,in longitudinal sections, i.e. in part FIG. 1A is an arrangement of abasic structure and a barrier layer placed in a set-up comprising a hardsupport and a soft pad, in part FIG. 1B is the arrangement of part FIG.1A after exerting pressure and elevated temperature and after removingthe soft pad, and in part FIG. 1C is the surgical implant taken from thesupport,

FIG. 2 an exploded three-dimensional view of an embodiment of thesurgical implant according to the invention,

FIGS. 3A and 3B show three-dimensional scanning microscopic images oftwo embodiments of the surgical implant according to the invention,which differ slightly due to manufacturing conditions, seen from theside where a film (barrier layer) is attached, and

FIG. 4 a schematic depth profile contour map of the embodiment accordingto FIG. 3A.

The structure of the surgical implant according to the invention can bebest understood by means of an example illustrating a manufacturingprocess of the implant, see FIGS. 1A, 1B and 1C in which the finishedsurgical implant is designated by reference numeral 1. FIGS. 1A, 1B and1C shows schematic views in longitudinal section.

In FIG. 1A, an arrangement of a basic structure 2 and a barrier layer 4is placed between a hard support 6 and a pad 8, which is softer than thesupport 6.

The basic structure 2 may be designed as, e.g., a surgical mesh or amesh-like sheet. In any case, it is areal (i.e. generally flat) andflexible. In FIGS. 1A, 1B and 1C, the dimension of the area of the basicstructure 2 not shown in the figure extends perpendicularly to the planeof the paper. Moreover, the basic structure 2 comprises pores 10surrounded by material 12. The pores 10 extend from a first face (side)14 to a second face (side) 16 of the basic structure 2. In theembodiment, the basic structure 2 is designed as a mesh-like sheet(made, e.g., by injection-molding or laser-cutting of polymeric films)so that the first face 14 and the second face 16 are essentially plan.If the basic structure is, e.g., a warp-knitted or crocheted surgicalmesh, the material 12 will be provided by filaments (monofilamentsand/or multi-filaments), and the first face 14 and the second face 16will be somewhat rougher because of the intersections of the filaments.

In the embodiment, the barrier layer 4 is made from a thin absorbablefilm without pores. In other embodiments, the barrier layer may comprisepores, which are generally smaller than the pores 10 of the basicstructure 2, however. According to FIG. 1A, the barrier layer 4 isplaced onto one side of the basic structure 2, which by definition isthe first face 14.

In the manufacturing process, the arrangement of the basic structure 2and the barrier layer 4 is heated and submitted to external pressure, asindicated by the arrow in FIG. 1A. The materials of the basic structure2 and the barrier layer 4 are appropriately selected such that the basicstructure 2 essentially keeps its shape while the material of thebarrier layer 4 get soft enough at the raised temperature so that it isurged, by the relatively soft pad 8, into the pores 10 of the basicstructure 2. Examples including more precise information on thematerials and the processing conditions are given further below. Thesoft pad 8 largely adapts to the depressions provided by the pores 10,while the support 6 defines a plane at the level of the second face 16of the basic structure 2 which is not traversed by the material of thebarrier layer 4.

FIG. 1B shows the result after the arrangement has been cooled to roomtemperature and the pad 8 has been removed. Inside the pores 10, thebarrier layer 4 forms barrier regions 18, which are largely plane andhave their outer face located (within tolerances due to themanufacturing process and the initial surface roughness of the basicstructure 2) at the level of the second face 16 of the basic structure2. At the edge zones of a given barrier region 18, the barrier layer 4rises, assuming a rather steep slope, and adjusts to the shape providedby the basic structure 2. The areas of the barrier layer 4 emerging fromadjacent pores 10 are connected to each other at the level of the firstface 14 so that the barrier layer 4 is coherent and able to fulfill itsbarrier function. FIG. 1C displays the finished surgical implant 1 whentaken away from the support 6.

FIG. 2 is an exploded three-dimensional view of an embodiment of thesurgical implant, here designated by 20. The surgical implant 20 may bethe surgical implant manufactured as explained by means of FIGS. 1A, 1Band 1C. It comprises a basic structure 22 designed, in the embodiment,as a flexible mesh-like sheet, and a barrier layer 24. It is wellvisible in FIG. 2 how the deformed regions of the barrier layer 24 fitinto pores 26 of the basic structure 22. In FIG. 2, the barrier regionsin the individual pores 26 are designated by 28. To improve theadherence of the barrier layer to the basic structure, a bondingmaterial can be used, which has a melting temperature lower than themelting temperature of at least part of the material of the basicstructure and lower than the melting temperature of at least part of thematerial of the barrier layer. In the manufacturing process, the bondingmaterial melts or gets very soft so that it acts as a kind of melt glueconnecting the barrier layer to the basic structure. The bondingmaterial may be incorporated in the basic structure and/or the barrierlayer, see also the following examples.

EXAMPLE 1

A large-pored composite mesh of polypropylene monofilament fibers andpoly-p-dioxanone (PDS®) monofilament fibers serving as a basic structurewas placed on a tenter frame form on top of a hard support surface. Anapproximately 10 μm thick film of MONOCRYL® (see above) serving as abarrier layer was placed on top of the basic structure, followed by asoft silicone foam pad covered by a metal plate. This assembly wasplaced in a hot press at 10 bar heated up to 120° C. for a couple ofminutes and cooled down at the same pressure. Under these conditions,the poly-p-dioxanone fibers of the basic structure acted as a melt glueto attach the barrier layer to the basic structure.

The barrier layer entered the pores of the basic structure, as describedabove (FIGS. 1A, 1B and 1C). Typical dimensions in the pore area of thesurgical implant obtained in this way were: pore diameter (clear width)1.71 mm, pore diameter (width measured between the centers of the meshfilaments defining the pore) 2.47 mm, diameter of largely flat barrierregion in the pore 1.53 mm (about 90% of pore diameter).

In an optional second step, a marker cut from a thick film (150 μm) ofviolet poly-p-dioxanone was heat-laminated on top of the barrier layerin order to enable an easy distinction of both faces of the implant.

In a marker-free area, the thickness of this surgical implant wasmechanically determined to be about 340 μm, about 10 μm thereofcontributing to the film. The depressions in the pores forming thebarrier regions had a depth, measured from the side of the first face(see FIGS. 1A, 1B and 1C) of up to 270 μm (when measured down frommaxima due to raised structures like knots of the mesh), with an averagedepression depth of about 60% of the thickness of the implant. When seenfrom the other side, i.e. the side of the second face, some fibers andknots of the basic structure where exposed beyond the second face of thefilm layer by up to about 185 μm.

The average roughness S_(a), defined as explained in detail furtherabove, of both sides of the implant was determined by means of anoptical scanning microscope of the type “Keyence Macroscope VR-3200”using standard settings adapted to measure the average roughness. On theside of the first face (film side, visceral side), the average roughnesswas 49 μm; on the side of the second face (mesh side, parietal side), itwas 28 μm. For both sides, the mean surfaces were determinedindependently of each other. Thus, on the parietal side, the implant wasconsiderably smoother, in spite of the fibers and knots emergingrelatively far from the second face of the film layer. Generally, thesefibers and knots are relatively small structures and do not contributemuch to the average roughness as defined above.

An oval test article of about 15 cm×10 cm was cut from this surgicalimplant and was intraperitonially placed in a pig, with the second face,i.e. the side on which the filaments of the basic structure were exposed(reference numeral 16 in FIG. 1C), facing to the peritoneum. The implanteasily attached to the peritoneum, holding its own weight including amarker, but could be repositioned and placed at different locations(more centrally and more laterally) without problems. The area weight ofthis test article was 68 g/m².

EXAMPLE 2

A surgical mesh of polypropylene filaments (basic mesh of Physiomesh®hernia repair implant of Ethicon, i.e. Physiomesh® without MONOCRYL®,film) serving as a basic structure was placed on a supported hardsilicon film covered by a baking paper in a form having pins for meshfixation. After a corona treatment of the polypropylene mesh, apre-laminate containing an 8-μm PDS® film (serving as melt glue) and a20-μm MONOCRYL® film (serving as barrier layer) was placed on the mesh,with the PDS® side facing to the mesh. This assembly was covered with asoft silicone pad, and the form was closed with a metal plate. After aheat lamination step in a press at 120° C. for 5 minutes, the assemblywas taken out of the press, cooled down between two cold metal platesfor about 20 minutes, and finally taken out of the form.

In the resulting surgical implant, the MONOCRYL® film had assumed amesh-like texture, as determined by the basic structure, with basicallyflat barrier regions in the respective pores having a width of about 1.5mm and a depth (measured from the first face 14, see FIG. 1C) of about200 μm to 230 μm.

The average roughness S_(a) (see Example 1) of this surgical implant was44 μm on the film side and 37 μm on the mesh side.

EXAMPLE 3

A TiO₂Mesh™ of Biocer GmbH (large-pored mesh warp-knitted frompolypropylene monofilaments having their surface coated with titandioxide) serving as a basic structure was covered with a pre-laminatecomposed of a 5-μm PDS® film (serving as a melt-glue) and a 20-μmMONOCRYL® film serving as a barrier layer, with the PDS® film sidefacing to the mesh. Any further surface treatment was not performed.This assembly was placed between a baking paper (mesh side) and a softpad (film side) in a heat press at 10 bar, heated up to 120° C. forseveral minutes and cooled down under pressure to about 50° C.

After removing the surgical implant obtained in this way from the press,it was macroscopically evaluated. The film side felt rough and the meshside felt smooth. Mesh and film were firmly connected to each other. Onthe film side, the topography of the film followed the essentiallydrop-like shape of the mesh pores, with flat barrier regions essentiallyfilling the pores completely.

The surgical implant had a total thickness (mechanically determined) of556 μm. The basically flat barrier regions of the film were located at adepth of up to 487 μm. The areal weight of the surgical implant was 90g/m².

When placed at an abdominal wall with the mesh side facing the abdominalwall, the clinging effect of this surgical implant is due not only tothe barrier regions in the pores, but also to the hydrophilicity of theTiO₂ coating of the mesh. In a test with a moist peritoneum of a pig,the implant adhered good enough to hold its own weight.

FIG. 3A shows a close-up three-dimensional view of the surgical implant(designated by reference numeral 30) manufactured as described above,taken by a scanning microscope from the film side (first face 14according to FIG. 1C). The shape of the basic structure 32 is clearlyvisible because the barrier layer 34 closely attaches to the filaments36 of the basic structure 32. Since the basic structure 32 iswarp-knitted, points 38 of intersecting filaments form peaks. In thepores 40, barrier regions 42 of the barrier layer 34 located generallyat the level of the other side of the basic structure 32 (second face 16according to FIG. 1C) are relatively large, filling most of the area ofa respective pore 40.

A surgical implant 30′ shown in FIG. 3B was manufactured in almost thesame way as the surgical implant 30 of FIG. 3A, the manufacturingconditions being only slightly different. Since a baking paper was notused, the barrier regions were slightly smoother. And since the pressurewas somewhat lower, the barrier layer did not approach the sides of thefilaments as closely as in the example according to FIG. 3A.

The average roughness S_(a) (see Example 1) of the surgical implant 30(FIG. 3A) was 79 μm on the film side and 48 μm on the mesh side. For theimplant 30′ (FIG. 3B), it was 83 μm on the film side and 60 μm on themesh side.

In surgical test procedures with pigs, both implants 30 and 30′ adheredto the peritoneum.

FIG. 4 is a depth profile contour map of the surgical implant accordingto FIG. 3A.

EXAMPLE 4

Omyra® Mesh (B. Braun), an orientated cPTFE film having multiple poresin the mm range, as a basic structure was coronatreated on one side inorder to render the surface acceptable for lamination and was coveredwith a pre-laminate composed of a 5-μm PDS® film and a 20-μm MONOCRYL®film with the PDS® film side facing to the cPTFE film, the MONOCRYL®film serving as a barrier layer and the PDS® film serving as a bondingmaterial. The assembly was placed between a hard pad (metal platecovered by baking paper on the cPTFE side) and a soft pad (MONOCRYL®film side) in a heat press at 10 bar, heated up to 120° C. and cooleddown under pressure to about 50° C. After taking the surgical implantobtained in this way out of the press, the barrier layer was dimpled.

Laser scan microscopic evaluation showed film depressions of up to 178μm and a total implant thickness of 201 μm, which means that the barrierlayer film having a thickness of about 20 μm was completely impressedinto the pores of the basic structure. Backside measurement demonstratedthat the cPTFE struts, i.e. the material between the pores, were almostwithin the basically flat barrier regions of MONOCRYL®. Starting fromsuch a barrier region, the out-of-plane angles of the barrier layerincreased when approaching the struts, depending on the location withinthe pore, e.g. from about 35° to 39° and up to 48° or, in narrowsections of the pore, being in the order of 12° to 14°. The largely flatbarrier regions in the central area of a pore had small out-of-planeangles, in the order of less than 1°, and a typical size of 0.9 mm.

The average roughness S_(a) (see Example 1) of this surgical implant was48 μm on the film side and 24 μm on the side of the basic structure.

In a test, this implant was placed at a moist peritoneum of a pig, withthe cPTFE side facing the peritoneum. In spite of the generalhydrophobicity of PTFE, the adhesion forces between the peritoneum andthe implant were large enough to hold the weight of the implant (245g/m²), due to the clinging effect of the barrier regions of the barrierlayer.

EXAMPLE 5

Samples of a surgical implant comparable to that of Example 1 wereprepared in a rectangular size of 3 cm×5 cm with slightly rounded edges.Additionally, a circular dyed (violet) PDS® film disk of about 150 μmthickness was laminated centrally on top of the barrier layer of animplant.

Using samples of this implant, a rabbit peritoneal defect model wasapplied, as described in U.S. Pat. No. 8,629,314 B. Adhesion wasevaluated after 2 weeks, see Table 1.

When a sample was correctly placed, with the smooth mesh side (secondface 16 in FIG. 1C) to the abdominal wall and the ridged (rough) barrierlayer side (first face 14 in FIG. 1C) to the viscera, almost noadhesions occurred. Only one implantation site showed minor grade 1adhesion (12.5% incidence), the remaining test sites were free ofadhesion. When the implant was wrongly positioned, with the mesh sidefacing to the viscera, in 87.5% of the cases adhesion occurred, and inmore severe grades from 1 to 4.

Thus, the surgical implant according to the invention exhibited a goodadhesion reduction when correctly placed with the rough barrier layerside facing the viscera.

TABLE 1 In-vivo performance of samples of the surgical implant accordingto Example 5 in rabbits Treatment groups Adhesion Adhesion extent for (n= 8) incidence Grades 0 to 4 Sham control 8/8 (100%) 1: (2/8), 2: (4/8),3: (1/8), 4: (1/8) Barrier layer to viscera 1/8 (12.5%) 0: (7/8), 1:(1/8) Mesh side to viscera 7/8 (87.5%) 0: (1/8), 1: (3/8), 2: (2/8), 4:(2/8)

1-18. (canceled)
 19. A process of manufacturing a surgical implantaccording to claim 1, characterized by the steps: providing a flexible,areal basic structure having a first face and a second face and beingprovided with pores extending from the first face to the second face,providing a barrier layer having a first face and a second face, placingthe basic structure onto a hard support, the second face of the basicstructure facing the support, placing the barrier layer, with its secondface, onto the first face of the basic structure, placing a pad onto thebarrier layer, the pad being softer than the support, applying heat andpressure, thereby softening the material of the barrier layer, urging itinto pores of the basic structure, and attaching the barrier layer tothe basic structure.
 20. A process according to claim 19, characterizedin that a bonding material, which has a melting temperature lower thanthe melting temperature of at least part of the material of the basicstructure and lower than the melting temperature of at least part of thematerial of the barrier layer, is included in the basic structureprovided, preferably in the form of filaments comprisingpoly-p-dioxanone.
 21. A process according to claim 19, characterized inthat a bonding material, which has a melting temperature lower than themelting temperature of at least part of the material of the basicstructure and lower than the melting temperature of at least part of thematerial of the barrier layer, is included in the barrier layerprovided, preferably as a sub-layer comprising poly-p-dioxanone andlaminated to a sub-layer comprising barrier material having a highermelting point than poly-p-dioxanone.
 22. A process according to any oneof claim 19, characterized in that, after applying heat and before thepressure is relieved, the basic structure and the barrier layer arecooled.
 23. A process of intraperitoneally placing a surgical implantaccording to any one of claim 1 in a patient's body, comprising thesteps: introducing the surgical implant via a trocar sleeve into thebody, deploying the surgical implant, the second face of the basicstructure facing a patient's peritoneum, clinging the surgical implantto the peritoneum, fixing the implant on the peritoneum.